[Drug treatment of acute myelogenous leukaemia. Current options and future perspectives]. / Az akut myeloid leukaemia gyógyszeres kezelése. Jelenlegi lehetoségek, jövobeli kilátások.

Acute myelogenous leukemia is a heterogeneous disease. Recent molecular mutational analysis techniques have shed more light on different, genetically well characterised types of the disease. Treatment approach is uniform except for acute promyelocytic leukemia. Application of the "3 + 7" induction treatment has been the gold standard in the past 40 years. While the dose of cytarabine has not been changed, escalating daunorubicine dose in younger (<60 years) patients with good performance status to 90 mg/m(2) had a positive impact on overall survival. High dose chemotherapy is tolerated poorly in patients older than 60 years of age and, as treatment is not curative in the elderly, improvement of overall survival and quality of life remains the main goal of management in these patients. Low intensity treatment is beneficial and can provide additional advantage over supportive care. Innovative and targeted therapy approaches might give promise to better management of patients with acute myelogenous leukemia.

WT1 Expression in Adult Acute Myeloid Leukemia: Assessing its Presence, Magnitude and Temporal Changes as Prognostic Factors.

Expression of the gene Wilms tumor 1 (WT1) has been suggested as a marker of minimal residual disease in acute myeloid leukemia (AML), but literature data are not without controversy. Our aim was to assess the presence, magnitude and temporal changes of WT1 expression as prognostic factors. 60 AML patients were followed until death or the end of the 6-year observation period. Blood samples were taken at diagnosis, post-induction, during remission and in case of a relapse. Using quantitative real-time PCR, we determined WT1 expression from each sample, normalized it against the endogenous control gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and classified samples as negative, moderately positive or highly positive. We divided the patients into groups based on detected WT1 expression values, illustrated overall and disease-free survival on Kaplan-Meier curves, and compared differences between each group by the logrank test. Disappearance of WT1-positivity during chemotherapy had a favorable effect on survival. Interestingly, no difference was seen between the survivals of WT1-positive subgroups that expressed moderate or high levels of WT1 mRNA. A 1-log decrease in WT1 expression without becoming negative did not affect prognosis, either. Our results suggest that defining a cut-off value for WT1-positivity, rather than just using logarithmic figures of changes in gene expression, might have prognostic use in post-induction AML patients. We encourage further, larger-scale studies.

Late pulmonary complications of treating Hodgkin lymphoma: bleomycin-induced toxicity.

INTRODUCTION: Survival of Hodgkin lymphoma (HL) patients has significantly improved in recent decades. The current first-line therapy is doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) ± irradiation and may cause pulmonary toxicity. Strategies to reduce late toxicity as well as increase survival rate are of interest. PATIENTS AND METHODS: Pulmonary function of previously treated HL patients was collected over a 12-month period using St. George Respiratory Questionnaire (SGRQ), chest X-ray, dynamic inhalation lung scintigraphy and spirometry. RESULTS: A total of 137 patients' data were reviewed. Median time elapsed since diagnosis was 11 years (range was 2 - 30 years). Chest irradiation did not significantly worsen pulmonary function. Number of ABVD cycles with consequential bleomycin dose showed significant correlation with SGRQ total score in patients receiving ABVD plus chest irradiation (p = 0.01). Scintigraphy results correlated with bleomycin dose in patients receiving ABVD without chest irradiation (right side: p = 0.099, left side: p = 0.051). DISCUSSION: An additive negative effect of chest irradiation was not confirmed as reflected in the literature; however, increasing cumulative bleomycin dose worsened pulmonary function.

[Treatment of acute myeloid leukemia -- a single center experience (2007-2013)]. / Heveny myeloid leukaemiás betegeink kezelésével szerzett tapasztalataink (2007-2013).

INTRODUCTION: Mortality of acute myeloid leukemia is still 60-70% in young (<60 years) adults and 90% in elderly (≥60 years) patients. AIM: The aim of the authors was to analyse the outcome of treatment in their patients with acute myeloid leukemia. METHOD: From 2007 to 2013, 173 patients with acute myeloid leukemia were treated. Patients were classified according to the European LeukemiaNet prognostic guideline. Association between mortality and the type of acute myeloid leukemia (secondary or primary), dose of daunoblastin at induction of treatment, and the rate of minimal residual disease were investigated. RESULTS: The 5-year survival probability was 25% in young adults and 2% in the elderly. The survival was significantly influenced by these prognostic factors. The 5-year survival rate was 50% in the young, favorable prognostic group. The 90 mg/m2 daunoblastin dose was found to be beneficial. Addition of bortezomib to the standard induction protocol had an additional beneficial effect. CONCLUSIONS: The speed and depth of the response to induction therapy, and the initial white blood cell count had an apparent effect on survival.

WT1 overexpression affecting clinical outcome in non-hodgkin lymphomas and adult acute lymphoblastic leukemia.

The Wilms tumor 1 (WT1) gene has a complex role as a transcriptional regulator, acting as tumor suppressor or oncogene in different malignancies. The prognostic role of its overexpression has been well-studied in leukemias, especially acute myeloid leukemia (AML), but not in lymphomas. For the first time to our knowledge, we present a study demonstrating the correlation of WT1 expression and survival in various non-Hodgkin lymphomas. We also studied the prognostic implications of WT1 overexpression in adult acute lymphoblastic leukemia (ALL). In our sample of 53 patients--25 with diffuse large B-cell lymphoma (DLBCL), 8 with mantle cell lymphoma (MCL), 9 with peripheral T-cell lymphoma (PTCL), 2 with Burkitt's lymphoma, 2 with mucosa-associated lymphoid tissue (MALT) lymphoma, and 7 with B-cell ALL--, we measured WT1 mRNA from blood samples by quantitative RT-PCR, and divided the patients into subgroups based on the level of expression. Kaplan-Meier survival curves were drawn and compared using the logrank test. In the sample of DLBCL patients, the difference in overall and disease-free survival between WT1-positive and negative subgroups was significant (p = 0.0475 and p = 0.0004, respectively), and in a few observed cases, a sudden increase in WT1 expression signified a relapse soon followed by death. Disease-free survival curves in MCL and ALL were similarly suggestive of a potential role played by WT1. In PTCL, though WT1-positivity was detected in 4 out of 9 cases, it did not seem to affect survival. The few cases of MALT and Burkitt's lymphoma all proved to be WT1-negative.

[Current treatment of acute myeloid leukaemia in adults]. / A felnottkori heveny myeloid leukaemia korszeru kezelése.

Recent cytogenetical findings and novel molecular biology results of acute myeloid leukaemia have shed new lights of our understanding in the diagnosis and treatment of the disease. Acute myeloid leukaemia is not only represented by the wide variety of morphological and immunophenotypic diversity but also demonstrates cytogenetical and molecular biological heterogeneity of its own. It has an unfavorable prognosis, especially in the elderly. Overall survival of younger patients (<50-60 years) has increased in the past years due to high dose chemotherapy (daunorubicine, cytarabine). But in case of unfavorable prognostic factors (not only cytogenetical but also molecular biological characters of the disease), allogeneic stem cell transplantation is needed for successful overall outcome. Better understanding the biology of acute myeloid leukaemia could establish novel targeted therapies and help us eventually to cure the disease.